Rahima Zennadi, PhD

Associate Professor in Medicine
Associate Professor in Pathology
Campus mail 337MED Sci Res Bldg, Durham, NC 27710
Phone (919) 684-5378
Email address zenna001@mc.duke.edu

Sickle Cell Disease

My research investigations in Hematology address the disorders associated with abnormalities affecting cell membrane proteins involved in cell-cell interactions and their role in sickle cell vasculopathy. In sickle cell disease (SCD), recurrent obstruction of the microvasculature leads to serious life-threatening complications such as acute pain crises, acute chest syndrome, kidney failure and cerebrovascular accidents triggered by ischemic injury in multiple organs. Vascular occlusion is caused largely by adherence of sickle red blood cells and leukocytes to the vascular endothelium.  Prevention and reversal of established vascular occlusion in sickle cell patients are still a therapeutic challenge. We are testing the hypothesis that vascular occlusion-dependent leukocyte and endothelial cell (EC) activation and inflammation leads to the increased ischemic oxidative stress and subsequent oxidative tissue injury. We propose that generation of ischemic oxidative stress, via activation of various abnormal signaling mechanisms, creates a positive feed-back loop that further enhances vaso-occlusion, endothelial activation and inflammation in the vasculature in general, and in particular, in the brain, kidney and lung vessels. We believe that targeting these signaling mechanisms will not only have anti-vaso-occlusive effects, but may also reduce inflammation and ischemic oxidative stress-induced endothelial dysfunction. In addition, we are also investigating signaling mechanisms activated by stress erythropoiesis during erythroid cell proliferation and maturation in sickle cell disease.

Malaria

Up to 15 to 20% of patients with falciparum malaria die despite our best malaria treatments. We clearly need more effective treatments than current anti-malarial drugs alone provide. Adherence of Plasmodium falciparum-infected red blood cells is at the core of the pathophysiology of severe malaria, and could lead to abnormal endothelial function, a process also central to the pathology of severe malaria. Using unique set of pharmacologic tools we are trying to elucidate the signaling mechanisms leading to infected red cell adherence to the vascular endothelium and the effects of these mechanisms on the vascular endothelium, and how best to target the parasite Plasmodium falciparum for treatment of malaria.

Education and Training

  • Ph.D., University of Nantes (France), 1992
  • M.S., University of Nantes (France), 1989

Publications

Zennadi, Rahima, and Marilyn J. Telen. “Atypical Activation of Plasma Membrane-Bound ERK1/2 Is Associated with Regulation of Sickle Red Cell Adhesion to Endothelium.” In Blood, 116:122–122. AMER SOC HEMATOLOGY, 2010.

Scholars@Duke

Zennadi, Rahima, Ai Chien, Ke Xu, Milena Batchvarova, and Marilyn J. Telen. “Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium..” Blood 112, no. 8 (October 15, 2008): 3474–83. https://doi.org/10.1182/blood-2008-01-134346.

PMID
18664622
Full Text

Zennadi, R., L. De Castro, C. Eyler, K. Xu, M. Ko, and M. J. Telen. “Role and regulation of sickle red cell interactions with other cells: ICAM-4 and other adhesion receptors..” Transfus Clin Biol 15, no. 1–2 (February 2008): 23–28. https://doi.org/10.1016/j.tracli.2008.04.009.

PMID
18502676
Full Text

Nishimura, Jun-ichi, Angela D. Burnette, Sabah Oney, Milena Batchvarova, Martha Delahunty, Rahima Zennadi, Bruce A. Sullenger, and Marilyn J. Telen. “Blocking adhesion of sickle erythrocytes to endothelial P-selectin using an RNAaptamer.” In Blood, 110:51A-51A. AMER SOC HEMATOLOGY, 2007.

Scholars@Duke

Zennadi, Rahima, Benjamin J. Moeller, Erin J. Whalen, Milena Batchvarova, Ke Xu, Siqing Shan, Martha Delahunty, Mark W. Dewhirst, and Marilyn J. Telen. “Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo..” Blood 110, no. 7 (October 1, 2007): 2708–17. https://doi.org/10.1182/blood-2006-11-056101.

PMID
17609430
Full Text

Nishimura, Jun-Ichi, Angela D. Burnette, Milena Batchvarova, Shahid M. Nimjee, Rahima Zennadi, Bruce A. Sullenger, and Marilyn J. Telen. “Blocking adhesion of sickle erythrocytes to endothelial alpha V beta 3 using RNA aptamer..” Blood 108, no. 11 (November 16, 2006): 206A-207A.

Scholars@Duke

Zennadi, Rahima, Chloe Chien, Milena Batchvarova, and Marilyn J. Telen. “Interaction of activated sickle red cell LW with leukocytes induces leukocyte adhesion to endothelium via CD44-E-selectin..” In Blood, 108:361A-361A. AMER SOC HEMATOLOGY, 2006.

Scholars@Duke

Ko, M., L. M. De Castro, J. C. Jonassaint, M. Batchvarova, R. Zennadi, and M. J. Telen. “The relationship of plasma laminin levels to anemia and the effect of soluble laminin on sickle red cell adhesion in SCD..” In Blood, 106:657A-657A. AMER SOC HEMATOLOGY, 2005.

Scholars@Duke

Chien, A. C., R. Zennadi, L. M. De Castro, and M. J. Telen. “Adhesive characteristics of hemoglobin SC red blood cells..” In Blood, 106:23B-24B. AMER SOC HEMATOLOGY, 2005.

Scholars@Duke

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